Radiogenomic biomarkers for immunotherapy in glioblastoma: A systematic review of magnetic resonance imaging studies.

Background: Immunotherapy is an effective "precision medicine" treatment for several cancers. Imaging signatures of the underlying genome (radiogenomics) in glioblastoma patients may serve as preoperative biomarkers of the tumor-host immune apparatus. Validated biomarkers would have the potential to stratify patients during immunotherapy clinical trials, and if trials are beneficial, facilitate personalized neo-adjuvant treatment. The increased use of whole genome sequencing data, and the advances in bioinformatics and machine learning make such developments plausible. We performed a systematic review to determine the extent of development and validation of immune-related radiogenomic biomarkers for glioblastoma. Methods: A systematic review was performed following PRISMA guidelines using the PubMed, Medline, and Embase databases. Qualitative analysis was performed by incorporating the QUADAS 2 tool and CLAIM checklist. PROSPERO registered: CRD42022340968. Extracted data were insufficiently homogenous to perform a meta-analysis. Results: Nine studies, all retrospective, were included. Biomarkers extracted from magnetic resonance imaging volumes of interest included apparent diffusion coefficient values, relative cerebral blood volume values, and image-derived features. These biomarkers correlated with genomic markers from tumor cells or immune cells or with patient survival. The majority of studies had a high risk of bias and applicability concerns regarding the index test performed. Conclusions: Radiogenomic immune biomarkers have the potential to provide early treatment options to patients with glioblastoma. Targeted immunotherapy, stratified by these biomarkers, has the potential to allow individualized neo-adjuvant precision treatment options in clinical trials. However, there are no prospective studies validating these biomarkers, and interpretation is limited due to study bias with little evidence of generalizability.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 2.

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Advanced MR Techniques for Preoperative Glioma Characterization: Part 1.

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.

Combining Multi-Shell Diffusion with Conventional MRI Improves Molecular Diagnosis of Diffuse Gliomas with Deep Learning.

The WHO classification since 2016 confirms the importance of integrating molecular diagnosis for prognosis and treatment decisions of adult-type diffuse gliomas. This motivates the development of non-invasive diagnostic methods, in particular MRI, to predict molecular subtypes of gliomas before surgery. At present, this development has been focused on deep-learning (DL)-based predictive models, mainly with conventional MRI (cMRI), despite recent studies suggesting multi-shell diffusion MRI (dMRI) offers complementary information to cMRI for molecular subtyping. The aim of this work is to evaluate the potential benefit of combining cMRI and multi-shell dMRI in DL-based models. A model implemented with deep residual neural networks was chosen as an illustrative example. Using a dataset of 146 patients with gliomas (from grade 2 to 4), the model was trained and evaluated, with nested cross-validation, on pre-operative cMRI, multi-shell dMRI, and a combination of the two for the following classification tasks: (i) IDH-mutation; (ii) 1p/19q-codeletion; and (iii) three molecular subtypes according to WHO 2021. The results from a subset of 100 patients with lower grades gliomas (2 and 3 according to WHO 2016) demonstrated that combining cMRI and multi-shell dMRI enabled the best performance in predicting IDH mutation and 1p/19q codeletion, achieving an accuracy of 75 ± 9% in predicting the IDH-mutation status, higher than using cMRI and multi-shell dMRI separately (both 70 ± 7%). Similar findings were observed for predicting the 1p/19q-codeletion status, with the accuracy from combining cMRI and multi-shell dMRI (72 ± 4%) higher than from each modality used alone (cMRI: 65 ± 6%; multi-shell dMRI: 66 ± 9%). These findings remain when we considered all 146 patients for predicting the IDH status (combined: 81 ± 5% accuracy; cMRI: 74 ± 5%; multi-shell dMRI: 73 ± 6%) and for the diagnosis of the three molecular subtypes according to WHO 2021 (combined: 60 ± 5%; cMRI: 57 ± 8%; multi-shell dMRI: 56 ± 7%). Together, these findings suggest that combining cMRI and multi-shell dMRI can offer higher accuracy than using each modality alone for predicting the IDH and 1p/19q status and in diagnosing the three molecular subtypes with DL-based models.

Predicting Overall Survival Time in Glioblastoma Patients Using Gradient Boosting Machines Algorithm and Recursive Feature Elimination Technique.

Despite advances in tumor treatment, the inconsistent response is a major challenge among glioblastoma multiform (GBM) that lead to different survival time. Our aim was to integrate multimodal MRI with non-supervised and supervised machine learning methods to predict GBM patients' survival time. To this end, we identified different compartments of the tumor and extracted their features. Next, we applied Random Forest-Recursive Feature Elimination (RF-RFE) to identify the most relevant features to feed into a GBoost machine. This study included 29 GBM patients with known survival time. RF-RFE GBoost model was evaluated to assess the survival prediction performance using optimal features. Furthermore, overall survival (OS) was analyzed using univariate and multivariate Cox regression analyses, to evaluate the effect of ROIs and their features on survival. The results showed that a RF-RFE Gboost machine was able to predict survival time with 75% accuracy. The results also revealed that the rCBV in the low perfusion area was significantly different between groups and had the greatest effect size in terms of the rate of change of the response variable (survival time). In conclusion, not only integration of multi-modality MRI but also feature selection method can enhance the classifier performance.